Microfluidic Devices for Genetic Analysis and Gene Expression Studies

Author: Liu, Jian

Year: 2007

Degree: Dissertation (Ph.D.)

Advisor: Quake, Stephen R.

Committee Members: Goddard, William A., III; Baldeschwieler, John D.; Collier, C. Patrick; Quake, Stephen R.

Option: Chemistry

DOI: 10.7907/xnm0-4a75

Abstract

Microfluidic devices hold the promise of becoming the next-generation laboratory platforms by offering many possible benefits in chemistry, biology, and medicine. However, microfluidics is still in its infancy at present, requiring a great deal of work before it can become more than an active research field in academia. This thesis describes efforts by the author in developing microfluidic technologies for applications in genetics. Section I describes the development of miniaturized devices for genetic analysis. Successful nucleic acid amplifications by polymerase chain reaction (PCR) have been demonstrated within a reaction volume as small as 700 picoliters. In section II, the concept of a microfluidic matrix chip is described and has been experimentally realized to solve the "macroscopic/microfluidic" interface problem. The matrix chip also provides a flexible platform to perform combinatorial tests with high throughput performance. Section III presents an application example of the microfluidic matrix chip in gene expression studies, providing quantitative profiles of gene isoforms by alternative splicing in a high throughput manner. In the section IV, a microfluidic chaotic mixer has been developed to accelerate the process and enhance the hybridization signals of DNA microarray experiments. These devices represent significant advances in microfluidics, with the following goals achieved: improved sensitivity and reliability of assays, reduction of consumption of reagents or analytes into desired economies of scale, and dramatic reduction of the time and complexity of "hands-on" manipulations, therefore providing experimental results in a high throughput manner.

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